Cisplatin Chemotherapy in Non-Small Cell Lung Cancer

by National Cancer Institute

Combined data from five large randomized clinical trials confirmed that cisplatin-based chemotherapy extends survival for patients with stage II or stage III non-small cell lung cancer. The benefit did not differ with different chemotherapy regimens, and was not affected by variables such as age, gender, or tumor type.

Source

American Society of Clinical Oncology (ASCO) annual meeting, Atlanta, June 3, 2006.

Background

Several recent large, randomized clinical trials have confirmed earlier evidence that chemotherapy with platinum-based (carboplatin or cisplatin) drug combinations after surgery for non-small cell lung cancer (NSCLC) significantly increases survival. For patients whose tumors can be removed surgically, cisplatin-based chemotherapy after surgery is now considered the standard of care. However, it was not known if some chemotherapy drug combinations provide a greater benefit or if different groups of patients benefit more than others from chemotherapy.

The Study

The Lung Adjuvant Cisplatin Evaluation (LACE) combined data (called a meta-analysis) from 4,584 patients with NSCLC who enrolled in five randomized clinical trials of cisplatin-based chemotherapy. Patients in all five trials underwent complete surgical removal of their tumor. Then, depending on the trial, they were randomly assigned to receive either chemotherapy or observation only, or either chemotherapy and radiation therapy or radiation therapy only.

Chemotherapy regimens consisted of cisplatin and one or two additional drugs that varied between trials. The investigators compared the different types of chemotherapy with the effect on overall survival.

The investigators also looked at whether any variation in the benefit of chemotherapy could be seen with age, gender, performance status (a measure of how well a patient is able to perform ordinary tasks and carry out daily activities), type of surgery, type of tumor, tumor stage, associated drugs, planned radiation therapy, and planned total dose of cisplatin.

The study was performed by the LACE Collaborative Group. The lead author is Jean Pierre Pignon, M.D., Ph.D., of the Institut Gustave-Roussy in Villejuif, France.

Results

The addition of chemotherapy after surgery provided a significant benefit in overall survival. The investigators found a 5.8 percent absolute increase in survival at three years after treatment, and a 5.5 percent increase at five years after treatment.

This increase in survival did not differ between different cisplatin-based chemotherapy regimens. The combination of cisplatin and vinorelbine provided a marginally better benefit than other drug combinations, but the dose of cisplatin given with vinorelbine was also higher than that given in other combinations. Therefore, the investigators could not rule out that the increase in cisplatin was responsible for the superior results of cisplatin and vinorelbine.

Out of all of the other variables examined, only the stage of the tumor affected the benefit seen with the addition of chemotherapy. Patients with stage II and III cancer received the largest benefit. Patients with stage IA disease did not benefit from the addition of chemotherapy, and in fact, chemotherapy may even negatively affect this group of patients. The data from patients with stage IB cancer also indicated that this group was not likely to substantially benefit from chemotherapy.

Limitations

While the LACE trial provided an important starting point for understanding the optimal use of chemotherapy after surgery for NSCLC, "given the number of questions yet to be answered, participation in [additional] clinical trials is key" said Joan Schiller, M.D., Chair of Hematology/Oncology at the University of Texas Southwestern Medical Center, in a discussion following presentation of the results at ASCO.

Additional trials will be needed to determine whether vinorelbine and cisplatin is really the most beneficial drug combination, or whether the dose of cisplatin matters more than the drug combination.

Comments

"We have good evidence that chemotherapy after surgery for stage II and stage III non-small cell lung cancer is beneficial," says lung cancer specialist Eva Szabo, M.D., of the National Cancer Institute's Division of Cancer Prevention, "but it remains to be seen whether we can identify subsets of patients with stage IB who can benefit as well. Further studies will be necessary."

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